Skyline Targeted Proteomics Environment

描述（由申请人提供）：随着蛋白质组学技术的成熟，这些工具被用来提高我们对人类和模式生物生物学中许多基础和临床问题的理解，最终目标是改进生物标记候选物验证的工作流程。为了解决这个问题，实验室已经证明，靶向质谱测量提供了一种有希望的替代基于免疫学的分析。这些实验的关键是处理仪器方法的生成和结果数据的后续分析的软件。我们开发了一个客户端软件工具来处理这些分析，叫做Skyline。在过去的2-3年中，Skyline已成为蛋白质组学中应用最广泛的软件工具之一。在这笔拨款中，我们建议继续开发和维护Skyline，该项目目前支持数百名研究人员进行基础科学、临床前和转化研究。具体来说，我们的建议有五个目标。1)在Skyline的数据结构和图形用户界面中增加对复杂实验模型的支持。2)支持Skyline内的校准曲线，复杂同位素反褶积，常规统计分析，以及Skyline架构内社区的新算法开发。3)支持全扫描MS1和MS/MS数据分析。4)支持靶向蛋白质组学库，并实现一个存储库来存储和传播靶向蛋白质组学方法。5)支持ThermoFisher三重四极杆质谱仪的自动方法优化和实时自动采集参数更新。

DESCRIPTION (provided by applicant): With the maturation of proteomics technologies, these tools are being used to improve our understanding of many basic and clinical questions in human and model organism biology - with the ultimate goal of an improved workflow for biomarker candidate validation. To handle this, laboratories have shown that targeted mass spectrometry measurements offer a promising alternative to immunological based assays. Critical to these experiments is software to handle the generation of instrument methods and the consequent analysis of the resulting data. We have developed a client software tool to handle these analyses called Skyline. In the last 2-3 years, Skyline has become one of the most widely software tools in proteomics. In this grant, we propose to continue the development and maintenance of Skyline, which currently supports hundreds of investigators in their basic science, pre-clinical, and translational research. Specifically, our proposal has five aims. 1) Add support for complex experiment models within Skyline's data structure and graphical user interface. 2) Support calibration curves, complex isotopomer deconvolution, routine statistical analyses within Skyline, and new algorithmic developments by the community within the Skyline architecture. 3) Support the analysis of full scan MS1 and MS/MS data. 4) Support targeted proteomics libraries and implement a repository to store and disseminate targeted proteomics methods. 5) Support automatic method optimization and real-time automatic acquisition parameter updates on ThermoFisher triple quadrupole mass spectrometers. PUBLIC HEALTH RELEVANCE: Mass spectrometry has been a fundamental technology for the analysis of proteins in health and disease. Laboratories have shown that targeted mass spectrometry measurements offer a promising alternative to immunological based assays that are the standard for quantitative protein measurements in clinical laboratories as well as basic research laboratories. Critical to these experiments is software to handle the generation of instrument methods and the consequent analysis of the resulting data so our software Skyline is a critical component to making targeted proteomics routine.